Dr. Steven G. Coca, from Yale University, New Haven, Connecticut, who worked on the analysis, told Reuters Health, “Given the fact that recent trials examining intensive glycemic control have shown no benefit for cardiovascular disease or all-cause mortality, trying to achieve tight glycemic control for the purpose of prevention of CKD may not be worth it due to costs, patient effort, hypoglycemic risks, etc.”
The seven trials he and his coworkers reviewed included 28,065 adults who were monitored for two to 15 years. The interventions to control blood sugar varied across the studies as did target hemoglobin A1C; the highest HbA1C target in the intensive arms of the trials was 7.1% and the lowest was less than 6%.
The median HbA1C values during the trials were lower in the intensive group in all studies and four studies achieved an HbA1C difference of more than 1% compared with the control group. In three studies, intensive glycemic control produced median HbA1C values of less than 7%.
After 163,828 patient-years of follow-up in the seven studies, intensive glucose control (compared with conventional control) was associated with reduced risk of micro- and macroalbuminuria (risk ratios 0.86 and 0.74).
However, intensive glycemic control did not reduce risk of several clinical renal end points, namely, a doubling of the serum creatinine (risk ratio 1.06), ESRD (risk ratio 0.69) or death from renal disease (risk ratio 0.99), the investigators report.
The pooled cumulative incidence of these three end points was low (less than 4%, 1.5% and 0.5%, respectively) compared with the surrogate renal end points of microalbuminuria and macroalbuminuria (23% and 5%, respectively).
Dr. Coca commented that “even if there is a true biologic benefit for prevention of CKD, the low absolute rates of CKD events makes the achievable absolute risk reduction via intervention very small, resulting in a very high number needed to treat to prevent one CKD event. Therefore, it will take a very large randomized controlled trial with long duration of follow-up to prove that intensive glycemic control is beneficial for CKD.”
In one of two invited commentaries on this study, Dr. David M. Nathan, of Massachusetts General Hospital and Harvard Medical School, Boston, says the studies included in this meta-analysis, with the possible exception of one “were far too brief to address the effects of intensive therapy on end-stage renal disease. Their short duration and low absolute rates of severe renal outcomes, acknowledged by the authors, preclude such an analysis.”
Dr. Nathan makes the point in his commentary that while “implementing intensive therapy is difficult and imposes burden and expense, all of the primary data continue to support its long-term benefit. We should be cautious not to abandon the goal HbA1C level of less than 7% for most patients.”
In the other commentary, Dr. Karen L. Margolis and Dr. Patrick J. O’Connor, of HealthPartners Research Foundation in Minneapolis, Minnesota, say this meta-analysis demonstrates “the lack of evidence that intensive glycemic control reduces the kinds of advanced complications of major concern to patients, such as renal failure.”
They conclude that for “many patients with T2DM, the potential benefits of multidrug intensive glucose control regimens, which are only marginally supported by current evidence, must be weighed against the potential risks of such therapy (including hypoglycemia and possible increased mortality risks) as well as the potentially larger benefits of focusing clinical attention on other domains, such as blood pressure lowering, lipid control and smoking cessation.”